Heteroatom ChemistryVolume 14, Number 4, 2003

Cycloaddition of Nitrile Oxides to SubstitutedVinylphosphonatesYong Ye, Guo-Yan Xu, Yu Zheng, and Lun-Zu LiuState Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry,Nankai University, Tianjin 300071, People’s Republic of China

Received 27 November 2002

ABSTRACT: Cycloaddition of nitrile oxides to sub-stituted vinylphosphonates was performed. A seriesof 4,5-dihydroisoxazoles containing phosphonyl groupwere synthesized under very mild condition in ex-cellent regiospecificity. C© 2003 Wiley Periodicals, Inc.Heteroatom Chem 14:309–311, 2003; Published onlinein Wiley InterScience (www.interscience.wiley.com). DOI10.1002/hc.10149

INTRODUCTION

Vinylphosphonates have been widely utilized in or-ganic synthesis during the last two decades and havebeen developed as a very useful template for the con-struction of functionalized organophosphorus com-pounds [1]. Much attention has recently been givento the development of new types of vinylphospho-nates and their synthetic applications [2, 3].

Recently, we discovered that 3-diethylphospho-noethylene reacts with nitrile oxides to afford re-giospecific products which are valuable interme-diates of the synthesis of variously functionalizedphosphonates [4].

As a continuation of this study, we report herethe behavior of vinylphosphonates substituted at

Correspondence to: Yong Ye; e-mail: yezhiyongmn@eyou.com.Contract grant sponsor: National Natural Science Foundation

of China.Contract grant number: 29972024.

c© 2003 Wiley Periodicals, Inc.

the 1-position by a phosphonyl or carbonyl group(1a,b), toward nitrile oxides. The reaction hasbeen explored with various p-substituted benzoni-trile oxides to achieve information on the influ-ence of the substituent upon the regioselectivity andreactivity.

RESULTS AND DISCUSSION

The reaction of 1a,b with benzonitrile oxides gen-erated in situ from benzohydroximoyl chlorides andtriethylamine in ether occurred smoothly at roomtemperature to afford the regiospecific products 2a–h in good yield (see Scheme 1). The cycloadducts2 were characterized by elemental analysis and 1HNMR spectra, and in part also by 31P NMR. Theirdata are shown in Tables 1 and 2. No regio-isomer could be detected. The direction of cycload-dition is as expected according to the PerturbationMO treatment of cycloaddition reactivity pioneeredby Sustmann [5a,b]. The compounds 2 represent themost favorable orientation because the 1,3-dipolarcycloaddition reaction is controlled by the inter-action between the LUMO of the dipole and theHOMO of the dipolarophile. The dipole LUMO hasits largest coefficient on carbon, and this becomesunited with the unsubstituted dipolarophile carbon,the site of highest HOMO coefficient for a variety ofsubstituents [5c,d].

Compared to the reaction of 3-diethyl-phospho-noethylene with nitrile oxides could be completed in36 h [4], whereas the reactions of 1a and 1b withnitrile oxides take place rapidly in 12 h. The moreelectron-deficient dipolarophiles react faster.

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310 Ye et al.

SCHEME 1

EXPERIMENTAL

Melting points are uncorrected. Elemental analyseswere carried on a Yanaco CHN Corder MT-3 appa-ratus. 1H and 31P NMR spectra were measured by

TABLE 1 Mp, Reaction Time (h), Yield (%), and Analysis 2a–h

Anal. Found (Calcd)

R mp Time Yield a C H N

2a H Oil 12 69.33 48.50 (48.69) 6.47 (6.49) 3.19 (3.34)2b 4-F 75–77 12 82.80 46.71 (46.69) 5.94 (5.99) 3.28 (3.20)2c 4-Cl 108–110 12 93.40 44.77 (44.99) 5.77 (5.78) 3.08 (3.09)2d 4-MeO 73–75 10 65.79 47.98 (48.11) 6.43 (6.50) 3.06 (3.12)2e 3,4-OCH2O Oil 10 74.70 46.60 (46.66) 5.92 (5.87) 3.03 (3.02)2f 4-MeO Oil 18 66.72 52.74 (52.99) 6.45 (6.28) 3.56 (3.64)2g 4-Cl Oil 24 90.50 49.18 (49.30) 5.42 (5.43) 3.32 (3.59)2h 3,4-OCH2O Oil 18 76.80 50.94 (51.13) 5.59 (5.55) 3.55 (3.51)

aIsolated yield based on 1a,b.

TABLE 2 1H NMR Data of 2a–h

1H NMR (ppm)

2aa 7.62–7.59 (m, 2H); 7.37–7.34 (m, 3H); 4.22–4.27 (m, 8H); 3.93 (t, 2H, J = 22.24 Hz); 1.24–1.32 (m, 12H)2b 7.60–7.67 (m, 2H); 7.04–7.23 (m, 2H); 4.22–4.33 (m, 8H); 3.93 (t, 2H, J = 23.67 Hz); 1.27–1.35 (m, 12H)2c 7.55 (d, 2H, J = 8.42 Hz); 7.39 (d, 2H, J = 8.41 Hz); 4.24–4.30 (m, 8H); 3.93 (t, 2H, J = 23.71 Hz); 1.28–1.36

(m, 12H)2d 7.57 (d, 2H, J = 8.68 Hz); 6.89 (d, 2H, J = 8.67 Hz); 4.21–4.30 (m, 8H); 3.93 (t, 2H, J = 23.59 Hz); 3.81 (s, 3H);

1.22–1.33 (m, 12H)2e 7.23 (s, 1H); 7.02 (d, 1H, J = 8.64 Hz); 6.8 (d, 1H, J = 8.62 Hz); 5.98 (s, 2H); 4.21–4.31 (m, 8H); 3.91 (t, 2H, J =

23.76 Hz); 1.27–1.35 (m, 12H)2f 7.57 (d, 2H, J = 8.41 Hz); 6.88 (d, 2H, J = 8.42 Hz); 4.24–4.31 (m, 6H); 3.96 (dd, 1H, J = 5.4, 20.5 Hz); 3.92 (dd, 1H,

J = 5.4, 22.6 Hz); 3.80 (s, 3H); 1.27–1.36 (m, 9H)2g 7.58 (d, 2H, J = 8.41 Hz); 7.36 (d, 2H, J = 8.41 Hz); 4.25–4.33 (m, 6H); 3.98 (dd, 1H, J = 6.48, 20.6 Hz); 3.93 (dd,

1H, J = 6.48, 22.7 Hz); 1.29–1.37 (m, 9H)2h 7.23 (s, 1H); 7.02 (d, 1H, J = 9.72 Hz); 6.79 (d, 1H, J = 9.72 Hz); 5.98 (s, 2H); 4.27–4.30 (m, 6H); 3.95 (dd, 1H,

J = 3.24, 20.6 Hz); 3.92 (dd, 1H, J = 3.24, 22.6 Hz); 1.26–1.37 (m, 9H)

a 31P of 2a is 18.71 ppm.

using a Bruker AC-P200 spectrometer with TMS and85% H3PO4 as the internal and external referencerespectively and with CDCl3 as the solvent. Solventsused were purified and dried by standard procedures.Compounds 1a and 1b were synthesized accordingto Ref. [6,7]. The hydroxamic chlorides were synthe-sized according to Ref. [8,9].

General Procedure for the Synthesis of 2a–h

To a stirred solution of 1a or 1b (2.0 mmol) and hy-droxamic chlorides (2.2 mmol) in dry ether (30 ml)under N2, a solution of Et3N (0.22 g, 2.2 mmol) indry ether (10 ml) was added dropwise at −10◦C. Themixture was stirred at room temperature until theconsumption of 1, monitored by TLC. Then, the re-action mixture was filtered to remove triethylaminehydrochloride and the solvent was evaporated in vac-uum. The residue was chromatographed on a sil-ica gel column with petroleum ether/ethyl acetate[3:1(v/v)] to give pure 2a–h as a white solid or oil.

Cycloaddition of Nitrile Oxides to Substituted Vinylphosphonates 311

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